Here's how I approach big cities, and preparing them to interact with the PCs;
1) as iserith said, describe the city as succinctly as possible. What is its character? What is it known for? What is it really like? What are the buildings made of (stone, brick, adobe, clay tile roofs, etc...)?
2) Break the city up into smaller districts. Make each district distinct in character, and understand how they relate to the overall character of the city. What makes this district different? Who lives here? What happens here? Why? Are the buildings here subtly/glaringly different? I like to create a map/sketch of the city at this level - even if it is only several blocks smushed together.
3) Then I like to look at the city from the other direction: Where do the poor live? the wealthy? the merchants? the foreigners/non-dominant races? If necessary, I adjust the flavor of the districts accordingly.
4) Prepare your set piece encounters/areas. If the PCs are here to meet the Governor, know where the governor's mansion/villa/palace is, what it is like, and what the people inside it are like,etc...
5) Prepare a few 1-2 sentence descriptions of some shops and inns, and their proprietors - don't place them anywhere, just have them ready. When the PCs look for an inn or a shop, adjust the descriptions as necessary to fit the district they are in. MAKE A NOTE where you put anything the PCs encounter, so you can come back to it later if you need to.
ALWAYS use Sights, Sounds, and Smells to describe where they are, and how they change as they move through the city. Use all three all the time.